1. 27.19 Secondary Structures of Peptides and Proteins

2. Levels of Protein Structure Primary structure = the amino acid sequence plus disulfide links Secondary structure = conformational relationship between nearest neighbor amino acids  helix pleated  sheet

3. Levels of Protein Structure planar geometry of peptide bond anti conformation of main chain hydrogen bonds between N—H and O=C The  -helix and pleated  sheet are both characterized by:

4. Pleated  Sheet Shown is a  sheet of protein chains composed of alternating glycine and alanine residues. Adjacent chains are antiparallel. Hydrogen bonds between chains. van der Waals forces produce pleated effect.

5. Pleated  Sheet  Sheet is most commonly seen with amino acids having small side chains (glycine, alanine, serine). 80% of fibroin (main protein in silk) is repeating sequence of —Gly—Ser—Gly—Ala—Gly—Ala—.  Sheet is flexible, but resists stretching.

6.  Helix Shown is an  helix of a protein in which all of the amino acids are L -alanine. Helix is right-handed with 3.6 amino acids per turn. Hydrogen bonds are within a single chain. Protein of muscle (myosin) and wool (  -keratin) contain large regions of  -helix. Chain can be stretched.

7. 27.20 Tertiary Structure of Peptides and Proteins

8. Tertiary Structure Refers to overall shape (how the chain is folded) Fibrous proteins (hair, tendons, wool) have elongated shapes Globular proteins are approximately spherical most enzymes are globular proteins an example is carboxypeptidase

9. Carboxypeptidase Carboxypeptidase is an enzyme that catalyzes the hydrolysis of proteins at their C-terminus. It is a metalloenzyme containing Zn 2+ at its active site. An amino acid with a positively charged side chain (Arg-145) is near the active site.

10. Carboxypeptidase Disulfide bond N-terminus C-terminus Zn 2+ Arg-145 tube model ribbon model

11. What happens at the active site? H3NH3NH3NH3N peptide O NHCHC + C R O O – H2NH2NH2NH2N H2NH2NH2NH2N C Arg-145 +

12. What happens at the active site? H3NH3NH3NH3N peptide O NHCHC + C R O O – H2NH2NH2NH2N H2NH2NH2NH2N C Arg-145 + The peptide or protein is bound at the active site by electrostatic attraction between its negatively charged carboxylate ion and arginine-145.

13. What happens at the active site? H3NH3NH3NH3N Zn 2+ peptide O NHCHC + C R O O – H2NH2NH2NH2N H2NH2NH2NH2N C Arg-145 + Zn 2+ acts as a Lewis acid toward the carbonyl oxygen, increasing the positive character of the carbonyl carbon.

14. What happens at the active site? H3NH3NH3NH3N Zn 2+ peptide O NHCHC + C R O O – H2NH2NH2NH2N H2NH2NH2NH2N C Arg-145 + Water attacks the carbonyl carbon. Nucleophilic acyl substitution occurs. O HH

15. What happens at the active site? Zn 2+ H2NH2NH2NH2N C Arg-145 + H3NH3NH3NH3N peptide O + C O – H 3 NCHC R O O – H2NH2NH2NH2N+

16. 27.21 Coenzymes

17. Coenzymes The range of chemical reactions that amino acid side chains can participate in is relatively limited. acid-base (transfer and accept protons) nucleophilic acyl substitution Many other biological processes, such as oxidation-reduction, require coenzymes, cofactors, or prosthetic groups in order to occur.

18. Coenzymes NADH, coenzyme A and coenzyme B 12 are examples of coenzymes. Heme is another example.

19. Heme N NN N Fe H3CH3CH3CH3C H3CH3CH3CH3C CH 3 CH 2 CH 2 CO 2 H CH CH 2 H2CH2CH2CH2CCH HO 2 CCH 2 CH 2 Molecule surrounding iron is a type of porphyrin.

20. Myoglobin N-terminusC-terminus Heme Heme is the coenzyme that binds oxygen in myoglobin (oxygen storage in muscles) and hemoglobin (oxygen transport).

21. 27.22 Protein Quaternary Structure: Hemoglobin

22. Protein Quaternary Structure Some proteins are assemblies of two or more chains. The way in which these chains are organized is called the quaternary structure. Hemoglobin, for example, consists of 4 subunits. There are 2  chains (identical) and 2  chains (also identical). Each subunit contains one heme and each protein is about the size of myoglobin.